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The title of this presentation is the role of bacteria and their toxins in retarding wound healing. Nothing in nature occurs in a vacuum. A real understanding of the role of bacteria and their toxins in retarding wound healing can only occur with a thorough understanding of the molecular and cellular pathways in a normal wound healing process.
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Production of this present lecture was made possible by an educational grant from Johnson & Johnson Wound Management, supplier of REGRANEX Gel, PROMOGRAN matrix, and ACTISORB silver 220 antimicrobial dressing. For more information about their fine products, stay tuned after the completion of the lecture where you will see a brief presentation about their company.
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Let me now discuss the outline for this presentation beginning with what is a wound or the definition of a wound. Next, let us talk about the definition of wound healing. Then, we will go on to the stages of the wound healing, angiogenesis, why wounds donât heal, factors affecting the balance of wound healing, principles of limb preservation, prevention and community education, the history and physical examination of the wound patient, the differential diagnosis of the lower extremity wounds, principles of ulcer management, a diagnostic and treatment algorithm, the impact of bacteria on wound healing, the bacterial continuum, the concept of critical colonization, bacterial toxins, decreasing bacterial levels, antimicrobial agents, and the silver cation plus activated charcoal as a model for the use of ionized silver in managing bacterial colonization and infection.
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A wound is simply defined as a clinical defect in soft tissue and/or bone and cartilage caused by trauma, ischemia, infection, and noninfectious inflammatory disorders. The common denominator in any wound is cell death.
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Wound healing is defined as a condition in previously injured tissue represented by removal of necrotic material, resolution of infection if it exists, and inflammation with organized collagen and mature epithelium is the final product.
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The stages of wound healing are a series of predictable molecular and cellular events shown here schematically in this diagram beginning with the stimulus for the process of wound healing being either an injury or an infection followed by the coagulation process, then the inflammatory process, the migration of fibroblasts and myofibroblasts, the proliferation of those cell types, the remodeling of the collagen produced by the fibroblast and myofibroblasts, and finally the epithelialization as the final component to the wound as we define it in a healed condition.
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If we look at the schematic of the stages of wound healing, again injury and infection as the stimulus, coagulation, inflammation, migration, proliferation, remodeling, and epithelialization, you can see that the process that we call angiogenesis is very much a linchpin, molecular and cellular process that controls the migration and proliferation which we have colored in red on the left to make them stand out as, again, key components and pivotal components of the healing process. I am going to talk about the concept of angiogenesis in a short while, but I think it is important to begin to see its central role in the stages of wound healing.
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Now, this slide shows the stages of wound healing again, but from a different prospective, i.e., along the time line beginning at the time of injury or infection and then progressing into hours, days, and weeks afterwards.
1. Notice the overlap of the coagulation inflammatory and then remodeling processes.
2. Note that the process of angiogenesis again affects the migratory, proliferative, and remodeling phases beginning again at hours progressing into days and even continuing into weeks along the healing process.
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Interactive question answer slide.
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In continuing the discussion of the stages of wound healing, let us now look at the role of the fibroblast, one of those key cell types that again is a pivotal cellular component to the wound healing process. You can see that the fibroblast is affected by many factors including growth factors from the surrounding tissues, cytokines, and certainly proteases, which can augment the movement and division of these fibroblasts in a positive way.
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Now here, we see the role of the keratinocyte. Remember that as the fibroblast is developing and producing collagen, the keratinocytes are migrating over the surface of the wound and maturing into final product that we need to have in a healed wound and that is the epithelialized wound. But notice how the protease release occurs as well with keratinocytes as it did with fibroblasts to dissolve nonviable tissue. Again, again you see the role of growth factors in the cell division and migration of the keratinocytes and finally angiogenesis again is a required factor because that is where blood flow is achieved for this very high metabolic rate both in the cell division and migration of the keratinocyte, as well as the cell division and collagen production of the fibroblast.
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This next slide is one of the series, actually a schematic showing the basic cell types and activity of a normally healing wound. You will notice the fibroblast in gray, the myofibroblast with its contractile elements in green, you will notice the alpha smooth muscle actin or stress fibers as they are called as the thin black horizontal lines. The arrows associated with the thin black lines are stress fibers contracting. The red lines are the capillaries. The red arrows are capillary budding, which is really the central function of the process we call angiogenesis. The later small cells are the keratinocytes and the mature epithelium derived from keratinocytes are the darker green cells schematics. The black bowtie shape is collagen, and the arrows associated with the keratinocytes demonstrate a process called lamellipodial movement or otherwise called epiboly.
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At the beginning of wound healing, we can see the proliferation of capillaries, this being the concept that I discussed earlier called angiogenesis. We also see the proliferation of keratinocytes, the synthesis of collagen, the contraction of the myofibroblast which contribute to the overall wound contraction, and also a phenomenon called lamellipodial movement or epiboly which has to do with the movement of the keratinocytes and distribution and expansion of the keratinocytes over the open wound to begin the process of maturation to form the final product of epithelialization which we see in the healed wound.
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Next in the sequence, we see in this schematic signs of wound contraction. Note that the myofibroblasts are contracting due to the alpha smooth muscle actin or stress fibers that are contained in them. We see continued angiogenesis. We see continued lamellipodial movement and maturation of keratinocytes into mature epithelium, and we see continued collagen synthesis and maturation of that collagen by realigning and linking of the collagen bundles which ultimately is needed for the strength of the completely healed wound.
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This next slide in the continuum of the normal wound healing process shows both the schematic above as well as a healing wound on the lower right. This wound is undergoing continued wound contraction, there is continued collagen synthesis, and there is continued maturation of the epithelium. This arrow shows the brighter red color of the wound, which is the non-epithelialized part of the wound still undergoing active mitosis of fibroblast and myofibroblast to produced collagen. Second arrow shows the more pale color of keratinocyte migration and maturation into the final epithelium of the wound, and you could notice the quite different color of these 2 tissues and in your mindâs eye you can see that this wound is healing at different rates. The most accelerated advanced part of the wound is around the edges, and of course, the keratinocyte bridge extending from left edge to right edge, which is approaching the final end product of mature epithelium.
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The next slide shows continued maturation of the epithelium. Next, it shows a new phenomenon called apoptosis or the reduction in the amount of fibroblasts and myofibroblasts visible in any cubic volume of a given wound. It also displays a decreasing angiogenesis and continued maturation of collagen. The apoptosis occurs, in a sense, because the collagen needs more room to develop, to reorganize, and now that the role of the fibroblast and myofibroblast is diminishing because more collagen is not needed to be synthesized, those fibroblast and myofibroblast begin the atrophy. Similarly, because there is less need for those cell types that are producing collagen, there is also less need for continuing angiogenesis; so that is why we see the blood vessel reduction in this schematic relative to the earlier schematics that showed an aggressive multiplication and division of fibroblast, myofibroblasts, and capillary cell budding.
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Relative question answer slide.
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This next slide shows continued maturation of the epithelium. You can see the more mature cells in the epithelium have a darker green, larger appearance. You can see a continued reduction in fibroblasts and myofibroblasts, that process we call apoptosis. There was a continued decrease in angiogenesis and a continued maturation of the collagen.
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The next slide shows continued maturation of the epithelium and the collagen. You will notice the more mature epithelium and you can observe fewer of the immature keratinocytes. There is a reduction in the vascularity of the wound, the continued reduction in the angiogenic process, and certainly a continued process of apoptosis due to the reduced need for collagen synthesis.
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As we approach the final healed wound product, we see a continued decrease in fibroblast and myofibroblast and proliferation. We see the continuation, however, of the collagen maturation and we also see the continued reduction in vascularity; and notice if you review these slides and go back and review them again, there is a sudden continuum occurring. Nothing is happening in leaps and bounds or om quantum leaps; it is a very subtle change in the cell types and the nature of the cell products like collagen and the organization and alignment of that collagen, and certainly in the maturation of the keratinocytes into mature epithelium.
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As we look at this slide, we see the continued collagen maturation, we see the reduction in visibility of the fibroblasts and myofibroblasts, and we see continued wound contraction occurring. Again, remember that the wound contraction has to do on a large part due to the stress fibers or alpha smooth muscle actin components that are very similar to the actin and myosin complexes in human skeletal muscle.
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Now, let us look at the wounds on the verge of healing, and you will see the arrows showing the mature epithelium in the schematic and also in the clinical wound that is more pale color by the arrow on the left, and then as the wound approaches complete healing, we can see that certainly the color of the wound changes but now the complete wound has mature epithelium on the right compared to the incomplete epithelium on the left. In a sense, the final maturation of epithelium and collagen is by definition what we call a healed wound.
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The next topic that I want to discuss is that fascinating concept of angiogenesis. Now, angiogenesis is defined as a growth of new blood vessels and it is an important natural process occurring in the body both in health and in disease. There is a fascinating website provided by the angiogenesis foundation in Cambridge, Massachusetts at www.angio.org that you can see on the slide and it is a tremendous insight into the various types of research including cancer research and wound healing research that are being approached through the final common pathway of the principles of angiogenesis.
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I am going to go over the sequence of fundamental steps in the angiogenic process beginning with diseased or injured tissues producing and releasing angiogenic growth factors that diffuse into the nearby tissues.
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The next thing that occurs is the angiogenic growth factors bind to specific receptors on the endothelial cells, represented by EC of nearby preexisting blood vessels.
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Once growth factors bind to their receptors, the endothelial cells become activated. Signals are sent from the cellsâ surface to the nucleus. The endothelial cellsâ machinery begins to produce new molecules including enzymes.
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These enzymes dissolve tiny holes in the sheath-like covering or basement membranes surrounding all existing blood vessels.
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The endothelial cells begin to divide or proliferate, and they migrate out through the dissolved holes of the existing blood vessel towards the diseased tissue.
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At this point, specialized molecules called adhesion molecules or integrins serve as grappling hooks to help pull the sprouting new blood vessels sprout forward.
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Additional enzymes called matrix metalloproteases or MMPs are produced to dissolve the tissue in front of the sprouting vessel tip in order to accommodate it. As the vessel extends, the tissue is remodeled around the vessel.
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Interactive question answer slide.
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Sprouting endothelial cells then roll up to form a blood vessel tube. This is what we begin then to recognize as a newly formed capillary.
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Individual blood vessel tubes then connect to form blood vessel loops that can circulate blood, and of course, normally we know that a capillary connects to a venule to complete the closed circulatory system.
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Finally, newly formed blood vessel tubes are stabilized by specialized muscle cells, i.e., smooth muscle cells and cells called pericytes that provide structural support to the system. Blood flow then can begin in this closed circulatory system.
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This histologic section of healing tissue shows a number of important items. Here, we see wound angiogenesis building granulation tissue. The histology here shows granulation tissue with new blood vessel growth. This section is stained for antibodies for alpha smooth muscle actin, and you can see the darkened area which represents the alpha smooth muscle actin staining demonstrating the importance of actin alpha smooth muscle actin in healing tissues, particularly in regards to wound contraction.
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In this slide, which again has colors in various stains to demonstrate the different cell types, normal capillaries are stabilized by smooth muscle cells and pericytes as I mentioned above. This is a laser confocal scan of a capillary showing endothelial cells in green, associated with smooth muscle cells and pericytes in red, and it is the smooth muscle cells and pericytes, of course, that form that all-important structural support or scaffolding for the endothelial cells that are actually carrying the blood vessels and the blood components.
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This next histologic section shows the result of excessive protease activity and how it can destroy angiogenic vessels. You will notice up top, there is normal angiogenic vessel production with sprouting from a collagen gel culture of rat aorta and you will see the normal integrity of all of these sprouting capillaries. In B below, however, you see that the vessels are fragmented and destroyed by prolonged exposure to proteases. Now remember, we talked about normal proteases occurring in order to cut through the tissue to allow new capillary budding during the angiogenic process. Well, the abnormal proteases or excessive metalloproteases is what causes all of the destructive events that we see in chronic hypergranulation tissue.
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Let us talk about the concept of a clean wound and why wounds do not heal. A clean wound is more than a wound that is just clean to the naked eye. It also means that there is no active infection or substantial critical colonization of the wound. It means no pressure that is unmanaged; no necrotic tissue including eschar, fibrinous exudate, and slough; it means no foreign bodies, no ischemic changes, no vasculitic processes, no abnormal metabolic processes for example uncontrolled systemic diseases such as diabetes; no malnutrition that is contributing to the wound healing, no uncontrolled edema, no underlying malignancy, and no wound-affecting drugs such for example steroids and nonsteroidal anti-inflammatory drugs which we know can affect the wound healing pathways.
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Now, let us looks at the concept of a chronic nonhealing wound from a different prospective. When we look at a chronic non-healed wound, we look primarily for sources of abnormal proteases and tissue damage including critically colonized or infected wounds. On the top photomicrograph on the right, we see the picture that is showed above of normal capillary development, that is the process of angiogenesis. When you add abnormal proteases, for example in a chronically infected wound, chronically necrotic wound, a vasculitic wound with a vasculitis that is not being controlled, you begin to develop destruction of the capillaries, destruction of the angiogenic process due to the excessive amounts of abnormal proteases because the balance of the wound has been disturbed. Again, we are not just looking at a wound without infection when we talk about a chronic wound. We are looking at some of the other factors that create that chronicity including abnormal uncontrolled pressure, necrotic tissue, foreign bodies, ischemia, vasculitis, abnormal metabolic processes, malnutrition, edema, malignancy, wound affecting drugs such as nonsteroidal anti-inflammatories and corticosteroids.
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Now, if we look at these factors that can affect the healing of a wound in a different way, i.e., we look at them as factors that will tip the scales in a sense towards healing or nonhealing and you can see if we line them up again including proper diagnosis, systemic disease, nutrition, and so on, we see that the plus and minuses represent a sort of a check-off list as we evaluate every patient and every wound to see which factors are contributing to healing and which factors are contributing to nonhealing. You can see the central role of bacteria and certainly its effect contributing to the chronicity and nonhealing of a wound.
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Now, let us move on to a brief review of the principles of limb preservation beginning with prevention, community education, a proper history and physical examination of the wound patient including wound assessment, differential diagnosis, and ultimately the final diagnosis of the cause of the wound, management of pain, management of nutrition including the physiology of wound healing as it relates to nutrition, the assessment of the patient who is being considered as a nutritional problem, and finally rules and pathways for proper supplementation of the malnourished wound patient. Next, we will talk about pressure and off loading including shoes, orthotics, and prosthetics, and then management of systemic disease. After this, we will talk about management of infection and necrosis as the central theme in the management of the wounded patient including débridement, incision and drainage, culture and sensitivity, as well as appropriate antibiotic therapy. Next, we will review vascular evaluation including the arterial, venous, and lymphatic components of the vascular system. We will discuss the level of foot and ankle reconstruction, and the choices that occur in the logical decision-making when it comes to reconstructing the infected or necrotic foot. We will talk about soft tissue healing, and again, the choices for soft tissue coverage that have to be made and finally, we will talk about rehabilitation of the healed patient as well as secondary prevention measures. All of these items together compose the bullets with the highlights of what must be considered for a thorough limb preservation program, whether it be in a private office or in a large wound healing center at an outpatient facility at a hospital setting.
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Let us begin then with prevention and community education. This slide shows simply a triad of prevention and community education, early diagnosis, and early treatment as it relates to the fundamental needs of a community and a community of individuals who are at risk for lower extremity wounds. This simple model has been shown to work as effectively in a village setting, in a rural region, of our planet, as well as highly industrialized sophisticated medical community such as a large urban area in the United States.
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In addition to that simple model, some of the main components of a patient in community education program include program of education for patient self-examination and monofilament testing for neuropathy, education in proper basic wound care, screening programs for diabetes including hemoglobin A1c, blood pressure, and lipid evaluation as well as foot risk assessments, nutritional education about the role and proper techniques for exercise, and of course smoking cessation as one of the cardinal rules in preventing wounds and healing wounds, particularly in a diabetic population.
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Interactive question answer slide.
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Moving on from prevention and community education, I want to now talk about the importance of the history and physical examination in the overall plan of a program of limb preservation. Included in this discussion under history and physical examination will be wound assessment, differential diagnosis, and obviously the importance of ultimately making a final diagnosis. The other aspects of the principles of limb preservation including pain, nutrition, pressure and offloading, management of systemic disease, infection and necrosis management, vascular evaluation, level of foot and ankle reconstruction, soft-tissue healing, rehabilitation, and secondary prevention will be discussed a bit later in the in the context of introducing the concept of a wound healing algorithm.
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Let us look a little more closely now at the components of a proper history and physical examination of the wound patient beginning with the history. The history should always begin with specific questions beginning with history of neuropathic and ischemic symptoms, previous wound or amputation; history of the wound in terms of its nature, onset, duration, location, and exacerbating factors, looking at the previous wound treatments including systemic medications, topical medications, mobility and weightbearing restrictions, previous history of débridement, and a history of tetanus prophylaxis.
Next, we move on to observations on the patientâs hygiene, the patientâs compliance, the patientâs general knowledge base, and an attempt to determine whether the patient is or has smoked for a period of time, is using drugs, alcohol, and consumes caffeine products such as coffee or tea.
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Continuing on for number 8, in the history are questions related to the patientâs medical condition, history of chronic diseases, a history of past and current medications that may be relevant to wound healing, the surgical history including a history of surgical procedures and types, and a history of the complications of those surgical procedures, particularly as it relates to wound healing of surgical wounds.
Next, review of the family history needs to be done, a review of systems, and finally a review of the patientâs allergies, particularly to medications.
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Next, we move on to the physical examination, which can be broken down into 2 main components; first, the general examination including examination of the patientâs mental status, neurologic status, cardiac status, respiratory status, abdominal examination, musculoskeletal examination, and general dermatologic examination. The second component of physical examination is a focused examination of the lower extremity including a dermatologic examination, and specifically, an examination of the wound and proper wound assessment, a neurologic examination including a sensory, motor, and autonomic examination, a thorough vascular examination, and a thorough musculoskeletal examination.
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Continuing to focus on the wound examination, let us talk about the fundamentals of proper wound assessment. It is extremely important that the woundâs length, width, and depth are measured every time the patient is seen and that these values are recorded for future comparison. An examination to see if there is any tunneling in the wound must be done, undermining, an examination to see if the wound probes to bone; and this is a very important and undisturbed part of the examination that really can help determine whether a patient may have osteomyelitis or not; and assessment of the base of the wound â is it a clean granulation tissue, is it a fibrinous exudate, is it a slough, is it eschar, is it purulent, and again is there exposed bone partially visible or palpable in the base of the wound, is there drainage either serous or sanguinous or purulent or some combination of these types of drainage, is there an odor to the wound, and finally is the wound painful. These are the main components for the proper wound assessment for any wound anywhere in the body.
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Expanding on the concept of wound assessment, I think it is very important to remind wound caregivers to use all of the senses to assess the wound. Odor can suggest the nature of an infection, for example, a very characteristic smell of a pseudomonas infection; probing the wound to asses for bony involvement and deep space involvement certainly can get a better picture of the type of wound problem that you are dealing with; and finally, identifying the tissues involved. Again, here in our photograph, you can see the arrow up top is pointing to normal intact skin, the next arrow moving downward shows hypergranulation tissue covered by fibrinous exudate, the third arrow coming down shows a devitalized extensor tendon to the third toe, and the fourth arrow is pointing towards the distal aspect of the third toe which is undergoing dry necrosis or dry gangrene as it is sometimes called.
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Finally, in looking at proper wound assessment, it is important to remember to examine wounds and the possible connections or sinus tracts between them. These sinus tracts can also be connected to the deep spaces. So when we see 1 or 2 or more wounds that appeared to be independent and removed from one another, remember that they may not only be connected by sinus tracts to each other, but they may be connected through sinus tracking to a more ominous deep space infection or necrosis.
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The next topic that I would like to include in our discussion, as you can see from the outline, is that of differential diagnosis of the wounds. Wounds can be classified simply into 3 categories; traumatic, infectious, and wounds from primary ulcerative disease. It is very important to consider multiple etiologies and not just one etiology when you are looking at a wounded patient. There is certainly a negative synergy that can occur with multiple wound etiologies, and these must be addressed. Multiple etiologies can accelerate the morbidity of any wound in the lower extremity. So, it is very important that the primary, secondary, and even a tertiary diagnoses is made so that all etiologies are systematically managed to optimize the healing rate of the wound.
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Let us look a little more closely at those 3 categories in our wound classification. First, under traumatic wounds, we can see that we place such wounds as lacerations, crush injuries, puncture wounds, bites, stings, pressure wounds, and iatrogenic wounds under this category. Next, under infectious wounds, we include abscesses, necrotizing types of wounds, T.E.N. or toxic epidermal necrolysis, wet necrosis or sometimes called wet gangrene, ecthyma, impetigo, and erythrasma. The final category of wounds, those from primary ulcerative disease, include a vascular I category or wounds caused by chronic PVD, a vascular II category caused by wounds with vasculitic etiologies, anesthetic wounds and under anesthetic wounds there are several types beginning with one of the common types that we see and that is diabetes. Anesthetic wounds can also be caused by Hansenâs disease or leprosy, syphilis, vitamin B-12 deficiency, heavy metal intoxication, pharmacologic causes, and alcoholism. The last three categories of wounds from primary ulcerative disease include dermatologic, purulent, and tropical. I think it is important to note, and that is why I highlighted diabetes in red on the slide, that diabetes is only one cause of wounds and it is certainly only one cause of anesthetic wounds. It is very important that we broaden our base of differential diagnoses to know all of the possibilities on a day-to-day basis that need to be ruled in or ruled out with appropriate testing so that we can make a thorough diagnosis.
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The next topic in our outline is principles of ulcer management, and first, we will talk about diagnoses. The first principle that I want to talk about is that diagnoses is essential because all wounds are not treated the same. Here, we have a picture of a sickle cell wound, next an ischemic wound, a wound from venous insufficiency, a neuropathic wound from a patient with diabetic neuropathy, a pressure wound in a nursing home patient, and in the lower right a wound from uncontrolled diabetic sepsis.
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Continuing on, we see an example of a squamous cell carcinoma of the leg, we see an iatrogenic wound from an injection of antibiotic in a web space infection. Here, we see a patient who is severely malnourished with a classic appearance of deterioration of soft tissue in a malnourished patient, and finally we see a necrotizing fasciitis in a diabetic patient.
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Second principle of ulcer management in regards to diagnosis is that many or possibly most wounds have multiple etiologies, but generally one dominant or primary etiology. The challenge is to determine the primary, secondary, and tertiary etiologies and plan treatments accordingly. The âlowering of the barâ phenomenon is when there is on coexisting wound factor that can augment one or more other factors to increase the risk of wound formation. Avoid the âRed Herringâ of diabetes as the only diagnosis, for example, ignoring coexisting neuropathy, subtle infection, venous disease, and malnutrition that may be significantly contributing to the deterioration or chronicity of this wound. You can see in the table in the bottom of the slide different combinations of wounds going from left to right that may have single, secondary, or sometimes even tertiary etiologies happening simultaneously that all need to be controlled in order for the wound to heal.
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Now, let us look at the treatment side of principles of ulcer management, and the first thing that is so important to discuss is that all wounds need certain basic treatments; for example, every patient needs treatment of an underlying systemic disease that is contributing to the nonhealing nature of a wound. Every wound needs infection management, every wounds needs débridement of necrotic tissue, every wounds need regular cleansing, and every wound needs regular redressing.
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Interactive question answer slide.
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Second principle of ulcer management regarding treatment is that certain wounds require special treatments and the avoidance of others. For example, sickle cell wounds need treatment of the primary anemia, and certainly, hydrocolloid and cadaveric xenografts may be a better choice compared to split thickness skin grafting because of the high rate of failure of split thickness skin grafts in this patient population. Also, neuropathic wounds certainly needs offloading, which is critical to putting these wounds on a healing path. Wounds from venous insufficiency need primarily management of the interstitial edema, and without this management, these wounds will not heal and will deteriorate. Vasculitic wounds need treatment of the underlying disease process, for example, rheumatoid arthritis, lupus, and scleroderma, and finally pressure wounds.
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So let us again look at a slide that I used earlier to sort of sum up the importance of proper diagnosis and management of systemic disease along with all of the other individual components of wound healing, which again will tip the scales and balance in favor of healing or in favor of nonhealing deterioration of the wound. Again, I think systematically if we approach these wounds in this way, our outcomes in terms of wound prevention and wound healing are going to be much better in the long run.
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The next section of discussion is the introduction of the concept of a diagnostic and treatment algorithm. An algorithm is simply a flow chart or a template or a methodology that is reproducible, which means that every patient that we see gets the benefit of having a very systematic, reproducible, thorough approach, both in terms of the history and physical examination as well as the differential diagnoses development, the ultimate diagnoses, and finally the treatment plan and rehabilitation as well as followup and prevention. That is all an algorithm is; it is a way of thinking and a way of thinking in a complete thorough manner, and you can see the algorithm begins with the history and physical examination. There are certainly prevention pathways which we have discussed earlier, but early on in our clinical approach to the patient, we certainly can look and evaluate the need for pain management, nutritional assessment and supplementation, and also at the end of this first slide of the algorithm the need for pressure management.
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In regards to proper data gathering and documentation, this slide shows a simple form that I came up with that I also ask my residents to use basically to keep themselves organized. It not only allows for a central location and document that keeps all of the basic information on our patients including labs and radiology results, but also for example can show who the consultants were for a particular admission on a patient so that if these are kept on file, they can be used in the future for referencing the proper consultant to ask in terms of maintaining continuity of care for our wound patients.
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The second slide of the algorithm begins with, again as we have discussed before, the importance of reviewing the systemic disease, condition of the patient, and finding out is the disease diagnosed, and if it is diagnosed, for example, diabetes, is it controlled or is it not controlled. Then, we must look at the importance of communication with the PCP or primary care physician or the endocrinologist or the appropriate internist, whoever is caring for the diabetes in this particular patient. You can see that as we continue to work on our differential diagnosis, we decide at this point whether we are trying to heal or palliate this wound; for example, a palliative patient would be a hospice patient who is terminal who we would not expect to put through all of the diagnostics and special procedures that we would in a patient whose wound we want to heal. Then, we begin to look at the infection and all of the components to assessing the patientâs infection and looking at other causes beside infection, for example trauma, malignancy, neuropathy, ischemia, and so on, ordering our labs, ordering our radiology exams, and special studies and again, continuing to mould and model and remodel the differential diagnoses.
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Now, we move on to the third panel of the diagnostic and treatment algorithm where we continue working with our diagnosis and begin to focus on the medical and surgical treatment of the infection and the necrotic tissue. Again, we have to decide what type of infection this is, is it a surgical infection meaning is there a necrotic tissue or abscesses to incise or drain, are there partial amputations or osteomyelitic bone to resect. This panel discusses the proper pathway and organization of the case including requesting other consultants like psychiatry, like anesthesiologists, like cardiologist, vascular surgeons and so on to complete the proper order of both diagnoses and treatment for our wounded patients.
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Now, I want to discuss briefly the concept of the wound energy burden. You will notice the unclean wound on the left where we see an increased energy burden. We see a clean wound on the right that has a decreased energy burden. If you can imagine in the wound on the left, just the bacterial burden alone beside the necrotic tissue; those bacteria are competing with the viable cells in that wound for oxygen and nutrients. So, you can imagine the competition that is going on, and the difficulty and the handicapped nature of the wound healing process in the left wound versus the right wound. The left wound also would be considered a chronic wound. The importance of surgical débridement is to create an acute wound from a chronic wound and put that wound back on a normal healing path and back to the normal stages of wound healing that we discussed earlier.
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This slide essentially shows an activated macrophage, which is one of the first cells to appear in the inflammatory phase of wound healing. The problem is the macrophage acutely is very much a friend to wound healing and responds to growth factors and will go in certainly as a mopping up, clean up function with bacterial necrotic tissue, and plays a role in the early phases of inflammation. However, when the macrophage is left to become chronic because there is chronic necrotic tissue or infection or vasculitis, the macrophage then in a sense turns on the patient and turns on the wound, and produces toxic oxygen metabolites, excessive amounts of proteases which destroy normal tissue, various types of amino-acid metabolites, and in a sense then starts to become a destroyer of the wound rather than enabler of healing. As you can see, the chronic infected necrotic wound on the left and then a wound that has become debrided and in that débridement process, those chronic macrophages are also physically removed by the active mechanical sharp débridement.
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The rationale for débridement is that the act of sharply debriding a wound decreases necrotic tissue, decreases the population of senescent cells, decreases nonmigratory cells and the bacterial load, and ultimately decreases the energy or the bioburden that we referred to earlier. Surgical débridement also improves intrinsic growth factors and also stimulates the processes of angiogenesis.
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Interactive question and answer slide.
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In discussing choices and types of débridement, I personally feel that sharp débridement is the first choice. I ask the question why invite the conversion of an acute wound to a chronic wound by delaying the production of a clean wound with a reduced energy burden. Enzymatic débridement is fine and can be used when sharp débridement is contraindicated or can be used subsequently to a sharp débridement for what I call micro-débridement of the wound for some short or more extended period. Thirdly, a wound must get larger before it gets smaller. You must remove all necrotic tissue and you must create the conversion of a chronic wound to an acute wound, and sometimes that means making the wound larger. You cannot be afraid to do that. The goal of every wound débridement is a bleeding base and a bleeding parameter with the removal of all necrotic, infected material, foreign bodies, and chronic granulation tissue. Finally, again, all of these wounds ultimately must be converted from the chronic pathway to an acute pathway, and the best and quickest way to do this is through sharp surgical débridement.
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Incision and drainage really is just a variation on the theme of débridement of all devitalized tissue. There is an old expression ânever let the sun set on an abscessâ. I think that is so important because the proteolytic enzymes and pus can be terribly destructive, and in a geometric manner destroy cubic volumes of tissue if left unchecked. So the importance of doing an incision and drainage certainly is to remove those destructive proteolytic enzymes. Taking that tissue or purulent tissue for culture and sensitivity certainly the tissue is much more appropriate or valuable than a swab culture. Be prepared for multiple debridements in incisions and drainages, and do not be hesitant to do that. High velocity pulse lavage with saline or saline with antibiotics is a hallmark of current standard of care to continue to debulk and reduce the bacterial burden of a wound, and certainly open packing of a wound is important to maintain proper channels for continued drainage of fluid and wound tissue after a débridement. This packing can be done on a daily basis or sometimes more than once a day depending on the volume of continued drainage from the wound.
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Osteomyelitis or infection in bone is something that many people are still convinced is not a healable condition. On the contrary, I feel that there are many possibilities for a cure in foot and ankle osteomyelitis. I think these wounds should be aggressively debrided, culture and sensitivities done, as well as bone sent for histology for comparison with the culture and sensitivity information, proper antibiotics need to be introduced into the treatment program whether they be oral, intravenous, absorbable, or nonabsorbable antibiotic beads, and finally bone can granulate and be skin-grafted successfully. If you think about bone as just another type of tissue, in many ways, it is very similar to soft tissue because the fundamental healing pathways again go back to the angiogenesis principles, and in freshly debrided raw bleeding cancellous bone, angiogenesis occurs, granulation tissue occurs, fibroblasts migrate, build collagen, and ultimately can build a bed upon which the split thickness skin graft can be applied.
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We are now at the point in the algorithm on that panel that discusses preoperative choices, and one of those choices is that of what kind of anesthesia will be used in a particular patient. Our choices of anesthesia include general, spinal, regional and under regional we certainly will include local infiltration, digital blocks, ray or mayo blocks both single and multiple, ankle blocks and a combination of popliteal and saphenous nerve block at the level of the knee.
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Again, when we look at the nerve distribution at the level of the knee, we see the popliteal nerve bifurcating to form the common peroneal nerve and the tibial nerve. When we add to that the purely sensory saphenous nerve, we can see that the popliteal and saphenous nerve block can essentially give complete anesthetic blockade below the level of the knee. Ankle blocks can be used when total foot anesthesia is required. Mayo or ray blocks can be used for metatarsal surgery and digital surgery. Digital blocks alone can be given when the toe is the only anatomic component of a particular procedure. Local infiltration can be used, for example, if small lesions, for example, warts or small superficial foreign bodies need to be excised or curetted.
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I want to discuss the tibial, common peroneal, and saphenous nerve block, also called the popliteal and saphenous nerve block. Again, reviewing the anatomy including the popliteal nerve bifurcating to form a tibial and common peroneal nerve in conjunction with a superficial block of the saphenous nerve can essentially provide total anesthesia below the level of the knee to the extent that even a below knee amputation could be done using this technique. I think this is an important alternative to spinal anesthesia. I think it is particularly valuable for the compromised patient not only for débridement, incision, and drainage, but also for foot and ankle reconstruction. A patient with severe reduction in ejection fraction due to severe cardiac disease would be a perfect candidate if he needed surgery of the foot, ankle, or leg to avoid the complications of spinal or general anesthesia. Certainly, we show that complete soft tissue and osseous anesthetic blockade can be achieved below the knee with a very little risk of complication.
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Here, we see our next panel of our algorithm that reviews decision-making in regards to antibiotics. There is also a reminder in this part of the algorithm to look for signs of malignancy and suggesting that biopsy be done on a regular basis in wounds that have not responded to normal treatment programs after 2 months. We can see here, in some cases, that proximal amputation is necessary due to certain types of malignancy or on the other hand a wide resection, for example, from a squamous cell carcinoma may be necessary which could subsequently be skin grafted. You will notice here the continuation of the palliative pathway on the hospice patient, and also in the lower part of the algorithm panel, you see the beginning of the vascular evaluation.
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The next panel discusses a thorough vascular examination and special study testing beginning with the clinical examination of pulses or the deficit pulses. We then move to noninvasive arterial Doppler testing with segmental pressures including toe pressures preferably, we look at the AVIs and based on your criteria, decide if a patient then needs an invasive arteriogram. Many different types of arteriograms exist, particularly types like CO2 arteriograms and patients who are allergic to the arteriographic dyes. Then, decisions are made as to the type of surgery that may be needed, for example angioplasties with the various subtypes versus different types of bypass, both proximal bypasses such as fem-pops and distal bypasses such as pop DP, pop PT, and even sometimes pop medial plantar artery bypasses. At this point on the panel, we are reminded that hyperbaric therapy may be indicated at this point for the marginally perfused patient or in a patient who may not be able to be bypassed. Finally, we look at the real need for edema management in these patients who sometimes have their edema neglected which really reduces the outcomes of healing in these patients who have both arterial and venous disease.
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The next panel discusses considerations for reconstruction and I think it is important that we look at the patient, treat the patient individually, and see first is this patient ambulatory, does he or she have ambulatory potential in the future, or is this patient a nonambulator which in many cases will possibly change the opinion as to the procedure of choice. We have to look at the patientâs condition of neuropathy in deciding on levels of amputation and types of reconstruction, for example, mid foot amputations, we have to look at the existence of any Charcot changes that may need surgical intervention, and decisions of conservative versus surgical management of Charcot changes would have to be made at this point. So, at the end of this panel in our thought processes, we have done the bony reconstruction, if any; the infection is managed, the vascularity is optimized; the patientâs pain, nutrition, and pressure is managed, and we are left with an open wound where we have to make final choices as to how this reconstructive foot will have the finished product of soft tissue healing achieved.
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This is 7th and last panel of the algorithm that discusses the plastic surgery and the choices for soft tissue healing. You can see that quite simply, the choices include simple flap closure, split thickness skin grafting, a combination of flap and skin graft, and finally choices of secondary healing which in many cases on the day-to-day basis is the way that we do heal wounds. If you see the subpanel, it is a secondary, which says débridement and products. Within this part of the decision tree, we make those decisions and the types of products that we use, both passive and active products; the active products being the more modern products such as growth factors and skin substitutes, but in conjunction with débridement or sometimes multiple débridement in those secondarily healing or granulating wounds. At this point, we also have to be reminded of the need to remove any bio-implantables such as polymethylacrylate beads with antibiotics that may have been implanted, and then pick the proper combination of simple or more complicated flaps, skin grafts, and/or secondary healing to achieve the ultimate result. You will also see in this panel that the palliative bypass ends here, which means that hospice patient gets the basic wound care including maintenance of a dry wound versus a wet wound, pain management, and pressure relief in an attempt to prevent the wound from deteriorating and certainly to prevent that suffering the hospice patient from getting new wounds, if possible. You can see the rehabilitation program continues and ends in this panel, for example, a patient that might have had a below knee amputation and a foot that was not salvageable, and you can see at this point the patient is discharged and will continue on hopefully in a loop of outpatient rehabilitation, skilled nursing care or home care, and certainly followup care in a wound center if necessary.
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Let us look now at the topic of the impact bacteria on wound healing, now that we have reviewed quite thoroughly the fundamental principles of wound healing and a basic approach through this particular algorithm introduced here to both diagnosis and treatment of lower extremity wounds. Impaired healing progress is one of the cardinal rules of the nonhealing infected wound. We know it is going to happen. We know that the wound will not continue on a normal wound-healing path through those stages of wound healing that I discussed above. One of the main reasons for this that we discussed earlier is that there is a competition between bacterial cells and local tissue cells for nutrients and oxygen. This is also an increased presence of inflammatory mediators and bacterial toxins, which degrade tissue components.
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Let us now look at the common bacteria found in wounds beginning with the common aerobes including staphylococcus aureus, the group D streptococci, the enterococci, and E. coli. The common anaerobes that we find are peptostreptococcus species, bacteroides fragilis, propionibacterium acnes, and the prevotella species. In the first 4 weeks in a wound generally, we see more domination of the aerobic gram-positive species. In the second 4 weeks or after the first 4 weeks, we find a more dominant population of anaerobic gram-negative bacteria.
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Looking at the effective bacteria on the wound, we can view it as somewhat of a mathematical equation where the infection, and I look at the infection synonymous with tissue destruction, equals the number of bacteria times the virulence of those bacteria divided by the hostâs immune function or capabilities.
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Now, let us go back to our original schematic, showing the basic steps in the normal wound healing process. That is beginning with the injury or infection which we are discussing now which stimulates the coagulation phase of wound healing, also stimulates the inflammatory phase followed by the migration, proliferative remodeling, and epithelialization phase. If you will notice that first trigger or that first stimulus for the wound healing process being either injury, infection, or both sets off this cascade of events, and if you look, one of the most important components to the continued normal inflammatory response with granulocytes, macrophage, and lymphocytes is the patientâs ability to resist infection because if the patientâs resistance is low, for example in chronic disease or cancer or malnutrition or diabetes which can effect the immune capabilities, the normal processes and pathways of wound healing will be delayed or completely retarded so that wounds will not heal. So, you can see underlined in red here how important resistance to infection is.
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This next slide again is familiar to us because it talks about the timeline and the overlap of the various stages of wound healing but also shows the effects of infection on those different processes and how, for example in the migratory and proliferative phase, you will see the typically that process eventually after several weeks, diminishes to zero. The problem is in the abnormal circumstance of continued unmanaged infection, that proliferative process can continue indefinitely and that is the source in many cases of what we call excessive or hypertrophic granulation tissue or chronic granulation tissue.
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Another slide that is familiar to us that was introduced earlier is the slide showing the relationship of the fibroblast with many of the other factors including growth factors and proteases that will affect its function during the healing process. If we now bring in infection and unchecked infection, the effect of infection and proteases and the increase in prolonged inflammatory response can completely destroy all of the positive interactions of growth factors and cytokines in the stimulation of normal fibroblastic cell division as well as collagen production.
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Similarly again, when we look at the keratinocyte, we see the same obstruction to normal keratinocyte division, migration, and ultimately maturation into the finished epithelial product in a healed wound because of those destructive forces and retarding forces caused by infection.
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Let us look at our original schematic again that shows the keratinocytes, the fibroblasts, the myofibroblasts, the smooth muscle actin fibers, or the stress fibers and the myofibroblasts and the new capillary growth that we call angiogenesis, but let us add 2 more components to this schematic; one is the necrotic tissue icon in grey and the bacteria icon in blue. Now, let us look at what happens to the normal wound healing process with the introduction of necrotic tissue and bacteria.
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You can see what has happened to our model-healing wound. The presence of necrotic tissue and bacteria has extended the proliferative phase, has increased the production of fibroblasts and myofibroblasts, has particularly increased the amount of new capillary growth because it is now unchecked angiogenesis, and you can see that the clinical manifestation of this is chronic granulation tissue, represented quite clearly in the schematic.
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In this slide, we see another variation on the theme of chronic infection and necrosis where instead of hypergranulation tissue produced by excessive angiogenesis, we see excessive collagen formation and ultimately, this would be abnormal scar caused by, for example, stitch abscess or some foreign body that produced excessive amounts of collagen because of excessive stimulation of fibroblastic activity and caused more scar tha, the wound really needed to heal, and of course, this scar could be more painful and cause medically unacceptable.
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This is a summary of the schematics, both showing the critically colonized wound with bacteria necrotic tissue below and what happens to that environment or that type of wound both, if it is treated properly meaning that bacteria are treated by various methods which we will talk about, and you can see the end product with proper treatment is the normal healing wound in the center, but with untreated bacteria different variations in terms of final wound products can occur to the common ones are chronic scar in the upper right and chronic hypergranulation tissue in the upper left.
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The concept of the bacterial continuum is important with understanding a practical approach to infection in wounds, and again, it is a continuum. There is not an âor nothingâ phenomenon. There is a continuum from the sterile wound to the contaminated wound and then moving to the right colonized wound and that important turning point in the wound known as the critically colonized wound that may not appeared to be infected to the eye of the clinical observer, but certainly is something that is a precursor to overt infection and needs to be treated. The problem is traditionally, those critically colonized wounds have been missed and these wounds have gone on to complete infection and further deterioration and tissue loss.
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So, critical colonization is the presence of bacteria on the wound surface to the extent that the healing process is compromised, but again, without the standard clinical signs of infection.
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When we look for signs of critical colonization, look at the wound shown here in this slide. The signs of critical colonization include bright red, friable granulation tissue, new areas of tissue breakdown, epithelial bridging, and/or to the wound, and a high exudate level. Often, the only sign of critical colonization may be the non-healing status of the wound.
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Interactive question answer quiz.
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So again, regarding critical colonization, we are talking about the situation where there is a presence of bacteria on the wound surface to the extent that the healing process is compromised, but without the standard clinical signs of infection. This condition or situation may delay healing via bacterial competition with tissue cells for oxygen and nutrients and production of bacterial toxins, and inflammatory mediators.
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In 2003, Philip G. Bowler wrote a fascinating paper with a much more modern approach and look at that traditional concept of the 105 bacterial growth guideline and the title of his paper was âTHE 105 BACTERIAL GROWTH GUIDELINE: REASSESSING ITS CLINICAL RELEVANCE IN WOUND HEALING.â
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In this paper, Bowler discussed the concept of the microbial ecosystem that really makes us look at the wound as a 3-dimensional cubic volume which has many-many factors trying to establish equilibrium including antibiotic resistance, aerobes, anaerobes, more virulent pathogenic bacteria vying for nutrients and oxygen, and certainly looking at the depths of the wound, a potentially dense population of bacteria in the deep components of the wound that may not be accessible if a simple swab culture is taken. and I think that is very-very much important concept. This is why we like to take tissue whether that be puss or soft tissue for culture particularly culturing the depth of the wound versus a much less valuable swab culture. And again, the complex microbial ecosystem in the wounds is shown here highlighting the potential for self-infection and cross contamination.
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So in Bowlerâs paper regarding critical colonization he makes some key points.
1. The challenge of diagnosing infection is chronic wounds is considerable and consists of evaluating a multitude of variables
2. By contrast, using a number, in this case the number of bacteria per grams of tissue is simple and straightforward, which may help explain the popularity and general acceptance of the 105 guideline or both acute and chronic wounds their differences notwithstanding.
3. Finally, his last key point, is that after reviewing the evidence to support this practice, the author suggests that wound infection should be diagnosed primarily on the basis of clinical signs and supported by microbiological observations.
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This diagram displays the importance of appropriate tissue biopsy for determining the true etiologic bacteria in a particular wound whether that be a single bacteria or a multiple bacteria. You can see that traditionally there has been an emphasis with surface sampling on semi-quantitative and qualitative microbiology. We need to provide a comprehensive profile of the wound _______. Unfortunately, swabbing the surface of the wound often leads to misleading results. Remember that the bio-burden and the microbial diversity is greatest in the deeper areas of the wound. Therefore control of the microorganism in this area is critical to minimize the opportunity for dissemination into deeper tissues and also to minimize the opportunity for cost contamination. So you can see that the deeper area of the tissue in green shows the true profile of the active bacteria that are doing harm to this wound. You can see progression of those bacteria to abscess formation if they are not treated both with debridement, lavage, incision and drainage, and proper antibiotics so that with deep tissue biopsy as opposed to the superficial swab technique traditionally done. There is an emphasis on quantitative microbiology. This isolates the cause of the microorganism or microorganism and it reflects a very localized microbial population that may be inconsistent with other parts of the wound so that it is important that the deep tissue of the wound be assessed properly and be used for proper culture and sensitivity. So these are the key aspects associated with superficial and deep tissue sampling.
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This diagram again shows that continuum of the bacterial profile of a wound and also the relationship of host resistance to the progression from contamination to an overtly infected wound. So again, this is the microbial continuum in wounds, that concept of critical colonization which needs to be treated because it is not only about to do damage but is beginning to do damage to those tissue of the wound even though to the naked eye clinically. With traditional observation techniques the wound does not look infected but it is considered critically colonized and certainly in need of both debridement and antibiotic therapy.
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I want to now discuss the concept of bacterial toxins. What are bacterial toxins? Basically, bacterial toxins are chemical substances produced by bacteria. These substances enable the bacteria to produce disease or adverse health effects in their host and the degree to which these toxins produce disease are called virulence factors.
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Interactive question answer slide.
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There are 2 major types of bacterial toxins, the first are exotoxins. The exotoxins are usually proteins. The second are endotoxins. Now, endotoxins are usually lipopolysaccharides with the abbreviation LPS.
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Let us discuss in further detail the bacterial exotoxins. Bacterial exotoxins are extracellular, soluble proteins. They are usually secreted by either Gram positive or Gram negative bacteria during the growth phase. Exotoxins can also be released when the bacteria are lysed. Thirdly, exotoxins attack specific target substrates in tissue or organs. Bacterial exotoxins essentially function the same way that enzymes function.
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This slide shows some of the common wound pathogen exotoxins beginning with those produced by staphylococcus aureus which includes toxic shock syndrome toxin or TSST-1, exfoliatin toxin, and enterotoxins. Second bacteria is pseudomonas aeruginosa which produces exotoxin A and thirdly, E. coli which produced LT toxin and ST toxin.
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Now, let us look at some of the bacterial endotoxins. These endotoxins, as mentioned earlier, are generally cell-associated lipopolysaccharides. They can affect cell wall structural components. They are usually associated strictly with gram-negative bacteria. They play a role in permeability and in biofilm production. They can be released when the bacteria are lysed by phagocytic cells and they can be released when the bacteria are attacked by certain antibiotics.
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What is the imp
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Lecture Hall
Wound Care | Science
